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| Identifier |
000419041 |
| Title |
An in vivo study of the role of Cytochrome P450 and Aldehyde Oxidase on Imidacloprid and Cypermethrin metabolism and related oxidative stress and DNA damage |
| Alternative Title |
IN vivo μελέτη του ρόλου του κυτοχρώματος P450 και της aldehyde oxidase στον μεταβολισμό του imidacloprid και του ypermethrin και εκτίμηση του οξειδωτικού στρές και βλαβών του DNA |
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Author
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Βαρδαβάς, Αλέξανδρος
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Thesis advisor
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Τσατσάκης, Αριστείδης
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Reviewer
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Carvalho, Felix
Τσατσαράκης, Εμμανουήλ
Θεοδωρόπουλος, Παναγιώτης
Τζαρδή, Μαρία
Νικιτόβιρσ-Τζανακάκη, Ντράγκανα
Τσιαούσης, Ιωάννης
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| Abstract |
In this PhD thesis we examined the toxicology aspect of two pesticides,
cypermethrin (CY) a synthetic pyrethroid and imidacloprid (IMI) a neonicotinoid
and their relevant functions, adverse effects and each pesticide’s more
dominant metabolic pathway. Regarding in vivo studies, many pesticides are
used in conjunction with Piperonyl Butoxide (PBO) as it is a powerful inhibitor
of the oxidative function of Cytochrome P450 (CYP450) and it is also known
for its synergistic actions when combined. PBO has become a diagnostic tool
for two important aspects of insecticide toxicology which is to determine if an
in vivo metabolism of an insecticide is oxidative and to determine if cases of
insecticide resistance involve oxidative metabolism by CYP450. The CYP450
mono-oxygenases are a large and functionally diverse family of enzymes that
carry out the initial oxidation of a wide variety of lipophilic compounds. These
enzymes play a major role in the metabolism of xenobiotics such as drugs,
pesticides, carcinogens and other environmental chemicals. It is also known
that the metabolites (produced when CYP450 is participated) of CYP450 are
responsible for toxicity damage arising from the use of pesticides. Furthermore,
neonicotinoids are simultaneously metabolized in vivo by aldehyde oxidase
(AOX) from the reduction of the nitro-imino group as well as by CYP450
oxidation reactions. Reduced AOX activity is closely correlated with reduced
IMI metabolism to IMI-NNO and IMI-NH, two main metabolic products from the
AOX pathway. Finally, metabolites from PBO and AOX reactions are believed
to be as potent as the parent compound. This thesis is based on a number of
studies each one designed to address a different aspect of the topic. In older
studies, CY has not been extensively studied regarding its combination with
PBO and neither has PBO been studied based on its inhibition capabilities
and its ability to induce toxicity on its own. These comparisons are described
in the first publication that focus on the systemic condition of New Zealand
male rabbits after long term exposure to CY and PBO based on oxidative stress
and telomerase activity test results. In the second publication, a continuation of
the first part of the study was conducted to evaluate additionally the liver and
kidney inflammation and genotoxicity in New Zealand white male rabbits after
long term exposure to CY and PBO. In the last publication, we evaluated the
inhibition effectiveness of sodium tungstate dihydrate (ST), an AOX inhibitor,
in order to elucidate the relative contribution of CYP 450 and AOX metabolic
pathways in IMI metabolism so as to clarify which metabolic pathway is actually
more detrimental in New Zealand male rabbits.
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| Language |
English |
| Issue date |
2018-12-05 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/6/d/d/metadata-dlib-1543568275-346451-26102.tkl
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